The aim of the current investigation is to investigate the acid-catalysed Fischer esterification mechanism underlying the synthesis of the anaesthetic benzocaine using p-aminobenzoic acid and ethanol in excess. The resulting synthesised compound was subject to IR and melting point analyses in order to determine the identity and indeed the purity of the obtained sample.
Benzocaine exhibits two main components common to the anaesthetic family: (1) an aromatic system usually having directly attached an ester and (2) a one to four unit hydrocarbon chain.
The ester group is essential in body detoxification of this substance due to enzymatic cleavage of the ester linkage. Other anaesthetics may also contain a tertiary amine functional group which translates into the compound being soluble in the body.
B. Stoichiometric Equations:
C. Reactant table:
M.W. (g mol-1)
Mole ratio theoretical/actual
65 mL = 51.42 g
1/31.1, in excess
5 mL = 9.15 g
0.025/0.036 = 0.69
The limiting reagent of this reaction is p-aminobenzoic acid.
Thus the theoretical yield of benzocaine is expected to be 0.036 mols as a 1:1 ratio exists between and 4-aminobenzoic acid and benzocaine.
% yield = =
= 69 % (2 S.F.)
No changes were made to the procedure given in CHEM3061 Laboratory Manual, p. 1-1 to 1-2.
Addition of concentrated sulfuric acid to the p-aminobenzoic acid, ethanol mix generated a white solid precipitate to form.
Addition of 10% sodium carbonate solution to the refluxed solution above caused effervescing to occur.
The product appeared to be a white crystalline solid, tabular, semi-transparent with moderate reflectivity, ~5mm in width.
Weight of product = 4.05 g % yield = 69 %
Melting point range = 88 – 89 ï¿½C Literature melting point = 89 ï¿½C
F. IR analysis:
1633, 1593, 1574
C=C-C aromatic ring stretch –
This is an approximation for the unique aromatic ring bonding.
2984, 2957, 2899
Aromatic C-H stretching
Diagnostic region confirming aromaticity.
770, 669, 639
Medium to strong
C-H out of plane bending on an aromatic ring
Multiple band structures; less energy required for C-H bending than for the its stretching counterpart and thus comes at a lower frequency.
1123, 1108, 1078, 1024
Medium to strong
C-H in plane bending vibrations of aromatic compounds
1,4 di-substituted (para) phenyl
Single, strong band between 860 – 800 cm-1 provides evidence to support a para substituted phenyl.
NH2 antisymmetric stretch
The asymmetric stretch is slightly higher in frequency than its symmetric counterpart as it requires more energy. Broad peaks due to H-bonding.
NH2 symmetric stretch
A smaller absorption near 3200 cm-1 is considered to be the result of interaction between an overtone of the 1600 cm-1 band with the symmetric N-H stretching band.
Aromatic primary amine CN stretch
Strong absorption due to large dipole moment between C and N.
Ester C=O stretch
Frequency observed is lower than normal ester C=O due to direct conjugation of the aromatic ring with the carbonyl.
C -O stretch
Polar bond – large dipole moment; strong absorption.
G. 1H NMR Analysis
Chemical shift (ppm)
Assignment of signals and explanation
Influenced to some extent by the electron withdrawing COO group causing deshielding and thus the chemical shift to move downfield from its original at approximately 0.8 ppm; this is an inductive effect.
Single peak observed in characteristic chemical shift region.
Influenced greatly by the electron withdrawing COO group causing deshielding and the chemical shift to move downfield from its original at approximately 1.2 ppm; this is an inductive effect.
Doublet of doublets
Influenced by the electron donating group NH2 which causes shielding and the chemical sift to move upfield of its original at approximately 7.2 ppm; this is a mesomeric effect. This effect obviously contributes more heavily than magnetic anisotropy, which in this case would produce the opposite effect; negative shielding would result, moving the signal downfield.
Doublet of doublets
Influenced by the electron withdrawing COO group causing deshielding and the chemical shift to move downfield from its original at approximately 7.2 ppm; this is an inductive effect. Also magnetic anisotropy causes negative shielding again contributing to the downfield move in chemical shift.
CHCl3 – residual protonated solvent
The reaction mechanism for the synthesis of benzocaine is divided into six key steps: (1) the protonation of the carbonyl by sulfuric acid to give a resonance stabilised intermediate; NH2 is also protonated (2) nucleophillic attack of the alcohol at the carbonyl carbon (3) loss of oxonium leaving group (4) proton transfer leading to a tetrahedral carbonyl addition intermediate (5) further proton transfer leading to a new oxonium ion and its subsequent loss giving (6) the acidified product, water and regeneration of the acid catalyst; finally the product is neutralised with sodium carbonate.
An acceptable yield of 69% of benzocaine was achieved in the present experiment; product may have been lost through (1) the reversible nature of each step in the reaction, although this was minimised by employing Le Chatelier’s principle (using excess ethanol) and (2) during refluxing, a loss of solvent would lead to a significant decrease in yield.
The identity of the synthesised compound was confirmed through IR and melting point analyses to be that of benzocaine. In particular, the obtained IR spectrum iterated the presence of structures such as a 1,4 di-substituted aromatic ring, primary aromatic amine, and an ester functional group directly attached to the aromatic ring as a result of lower frequency of the carbonyl than expected due to conjugation from the aromatic ring. Furthermore, the melting point range achieved (88-89ï¿½C) concurred well with the literature value of 89ï¿½C, confirming the purity of the obtained sample.
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